The central nervous system strictly regulates its blood flow in response to changes in systemic pressure or metabolic demand. Despite decades of intensive research on the subject, the mechanisms of blood flow regulation are not well understood. A multitude of endogenous tissue substances profoundly affects blood flow, including CO2, H+, K+, Ca++, many metabolic by-products, various peptides and neurotransmitters. There is little agreement in the literature concerning which, if any, of these factors play a major role in normal blood flow regulation. Although there is morphological evidence of sympathetic fibers innervating brain and spinal cord blood vessels, the physiological significance of these connections is controversial. Recently, in the course of studying blood flow in spinal cord injury, we found that 1) surgical ablation of the paravertebral sympathetic ganglia impairs normal autoregulatory responses to blood pressure changes and prevents the onset of ischemia that often accompanies severe spinal injuries; 2) there is a 40-60 mM increase in extracellular K+ after contusion injury and that post-traumatic ischemia occurred only after the K+ fell below 10 mM; 3) naloxone, a specific opiate receptor antagonist, ameliorates post-traumatic ischemia. We consequently hypothesized that the paravertebral ganglia play an important role in spinal cord blood flow regulation, that large increases in extracellular K+ may prevent vasoconstriction, and that at least part of the post-traumatic ischemia is mediated by endogenous opiates released by sympathetic fibers. We propose to study blood flow regulation in the uninjured cat spinal cord: 1) using the hydrogen clearance method to measure local blood flow while stimulating or after ablating segmental paravertebral sympathetic ganglia; 2) measuring extracellular K+, H+, Ca++ with ion-selective microelectrodes and correlating the ionic microenvironment with blood flow; 3) altering the ionic microenvironment of the cord by local superfusion of different ionic solutions and observing the effect on blood flow responses to blood pressure and respiratory changes; 4) examining the effects of locally applied opiates and opiate blockers on the blood flow responses. Our goal is to elucidate the mechanisms of blood flow regulation.